Tag-and-modify approach

Chalker JM, Bemardes GJL, Davis BG (2011) A tag-and-modify approach to site-selective protein modification. Acc Chem Res 44 730-741... 

Extensive work on the tag-and-modify approach has been carried out by the Davis group, ° spanning from the modification of a cysteine tag to the inclusion of non-proteinogenic amino acids (e.g. dehydroalanine,... 

Fig. 17 Thio- and seleno-glycoside derivatives used for the "Tag and Modify" approach. ...

The more successful strategy for the isolation of RNA- and DNA-based catalysts involves the direct screening of nucleic acids libraries for catalytic activity. This approach is called direct selection [6, 65, 77, 78, 86, 101-107]. In direct selections, nucleic acids that are capable of catalyzing a particular chemical transformation modify themselves with a tag or other characteristic that allows their preferential enrichment over those molecules which are catalytically inactive [108]. The design of ribozyme-selections involving reactions between two small substrates requires that one reactant be covalently attached to every individual member of the starting RNA pool. After the reaction with another substrate which usually carries the selection-tag has occurred, the self-modified RNA is immobilized on a solid support, separated from non-active molecules, and then cleaved off the support. 

In the ferrioxamine family, two approaches were followed one, based on modifying the amine at the end of the extended tail in the natural ferrioxamine B with an appropriate fluorophore the second, substituting biomimetic analogs 146-155 on either their amino or carboxy termini, to assess their chemical and biological differences. Both approaches were followed and two classes of compounds were prepared with various fluorescent tags. 

The limitation of this signal-off architecture was improved in another work [49] in which the aptamer was first allowed to interact with short partially complementary nucleotide modified by MB. (MB)-tagged oligonucleotide with aptamer formed rigid duplex that prevents the MB tag from approaching the electrode surface, so the reduction current is suppressed. The addition of thrombin resulted in quadruplex formation and approach of MB to the surface of electrode. Thus, the amplitude of reduction signal increased (Fig. 33.3D). This method allowed to detect thrombin at concentrations as low as 3 nmol/L. 

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